ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.-2C>A (rs202104448)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130810 SCV000185706 likely benign Hereditary cancer-predisposing syndrome 2019-01-23 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;Other strong data supporting benign classification
GeneDx RCV000422154 SCV000518135 likely benign not specified 2017-02-15 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Genetic Services Laboratory, University of Chicago RCV000422154 SCV000595912 uncertain significance not specified 2016-02-26 criteria provided, single submitter clinical testing
Color Health, Inc RCV000130810 SCV000904195 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000422154 SCV001432121 uncertain significance not specified 2020-08-24 criteria provided, single submitter clinical testing Variant summary: NBN c.-2C>A is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 1.2e-05 in 244888 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.-2C>A has been reported in the literature in at-least one individual undergoing clinical genetic testing based on a history of Lynch syndrome-associated cancer and/or polyps (Yurgelun_2015). This report does not provide unequivocal conclusions about association of the variant with Nijmegen Breakage Syndrome and/or NBN related cancer predisposition syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments and limited evidence (VUS, n=2, likely benign, n=2). Based on the evidence outlined above, the variant was classified as uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284195 SCV001469842 uncertain significance not provided 2019-11-04 criteria provided, single submitter clinical testing

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